Clinical Trials

Inclusion Criteria:

Substudy 1

• Subject achieved clinical response in Study M14-431 or Study M14-433.
• Subject completed Week 12 (in subjects who achieve response at Week 12) or Week 24 (in subjects who achieve response at Week 24) visit and procedures in Study M14-431 or Study M14-433. The final endoscopy for Studies M14-431 or M14-433 may be missing, if the endoscopy cannot be performed during the COVID-19 pandemic.
  • Note: Subjects completing Part 3/Cohort 3 of Study M14-431, who received open label Extended Treatment, should enroll in Substudy 2.

Substudy 2

• Subject completed Week 52 of the maintenance period of Study M14-430 (Substudy 1). Completion includes the Week 52 endoscopy of Substudy 1. The Week 52 endoscopy may be missing, if the endoscopy cannot be performed during the COVID-19 pandemic or any state of emergency or pandemic situation.
• Subject achieved clinical response at Week 24 and completed Week 24 visit and procedures in Part 3/Cohort 3 of Study M14-431.

Substudy 3

• Subject is an ongoing subject in Substudy 2 for at least 12 months.
• Subject has received open-label upadacitinib 30 mg QD for at least 6 months during Substudy 2.
• Subject is in stable remission for at least 6 months defined as:
  • CDAI < 150; AND
  • CRP < 5 mg/L and FCP < 250 mg/kg; AND
  • Subject has not been on locally acting (rectal or suppository) or systemic corticosteroids for CD ≥ 90 days prior to the entry of Substudy 3.
  • NOTE: Hematocrit for baseline CDAI calculation, CRP, and FCP should be assessed within 4 weeks prior to enrolment to confirm subjects are in stable remission at time of enrolment into the substudy and will serve as Baseline (Week 0) results.
• Subject has not received any new medication or increase of the dose of current concomitant medication for the treatment of CD in the past 3 months.

Substudy 1, 2 and 3

• If female, subject must be either postmenopausal, OR permanently surgically sterile OR for females of childbearing potential, practicing at least one protocol specified method of birth control that is effective from Baseline Visit through at least 30 days after the last dose of study drug.
• Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any study-specific procedures and comply with the requirements of this study protocol. In countries where the subject is 18 years-old but not of minimum adult age to consent according to local regulations, a subject's parent or guardian must be willing to provide written informed consent (e.g., Japan < 20 years old).

Exclusion Criteria:

Substudy 1, 2 and 3

• Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
• Subject who has a known hypersensitivity to upadacitinib or its excipients, or had an AE during Studies M14-431, M14-433, or Substudy 1 or 2 of Study M14-430 that, in the investigator's judgment, makes the subject unsuitable for this study.
• Subjects who anticipate the need for any live vaccine during study participation including at least 30 days (or longer, if required locally [e.g., 8 weeks for Japan]) after the last dose of study drug.
• Female subjects with a confirmed positive pregnancy test at the final visit in Studies M14-431, M14-433, or Substudy 1 of Study M14-430, or who is considering becoming pregnant during the study.
• Subject is not in compliance with prior and concomitant medication requirements throughout Studies M14-431, M14-433, or Substudy 1 or 2 of Study M14-430 per investigator assessment.
• Subject at the final visit of M14-431 or M14-433 with any active or chronic recurring infections based on the investigator's assessment makes the subject an unsuitable candidate for the study. Subjects with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed, and the infection is resolved, based on the investigator's assessment.
• Current evidence of active or untreated latent tuberculosis.
• Subjects with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Studies M14-431, M14-433, or Substudy 1 or 2 of Study M14-430.
• Current or history of malignancy or lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly; except for successfully treated non-metastatic cutaneous squamous cell, basal cell carcinoma, and/or localized carcinoma in situ of the cervix.
• Subject with a poorly controlled medical condition, such as uncontrolled diabetes, unstable ischemic heart disease, moderate or severe congestive heart failure, recent cerebrovascular accidents, and any other condition which, in the opinion of the investigator or sponsor, would put the subject at risk by participation in this study.
• Laboratory values from the visit immediately prior to the Substudy 1 Week 0 Visit or the Substudy 2 Week 0 Visit (for those subjects enrolling into Cohort 4) meeting the following criteria:
  • AST or ALT > 3 × upper limit of normal (ULN);
  • Total WBC count < 2,000/µ;
  • Absolute neutrophil count (ANC) < 1,000/µL;
  • Platelet count < 50,000/µL;
  • Absolute lymphocyte count < 500/µL;
  • Hemoglobin < 8 g/dL.
• Enrollment in another interventional clinical study while participating in this study.
• For Substudy 3 only: Total SES-CD > 4 and/or subscore > 1 in any segment in the Substudy 2 annual ileo-colonoscopy, if performed within 6 months prior to Week 0 in Substudy 3, based on the local reader score.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/25/23. Questions regarding updates should be directed to the study team contact.